Methamphetamine produces neurotoxicity in human methamphetamine abusers and in nonhuman primate and rat models. Methamphetamine neurotoxicity is characterized by significant depletions of dopamine and serotonin in the striatum and nucleus accumbens. Behavioral consequences include a decreased locomotor response to a subsequent challenge of methamphetamine and an enhancement of methamphetamine conditioned place preference. Environmental enrichment is a paradigm which has been used to study environmental control of response to drugs of abuse and to investigate the protective factors of enrichment on brain injury. Since methamphetamine use and methamphetamine-induced neurotoxicity are a considerable health concern, it is important to investigate the potential of environmental factors, including enrichment, in protecting against methamphetamine-induced neurotoxicity. The present experiments will assess whether or not environmental enrichment can protect against the neurochemical and behavioral consequences of methamphetarnine-induced neurotoxicity. It is hypothesized that environmental enrichment will protect against methamphetamine-induced neurotoxicity by reducing the amount of depletion of dopamine and serotonin, reducing the loss of functional dopamine release, and decreasing the behavioral consequences as assessed by methamphetamine conditioned place preference. If environmental enrichment is protective, this information could be useful in the development of drug prevention and treatment programs.